Five years of support are requested to create a faculty development program that will enable junior faculty involved in research at the three PhD granting institutions in Kansas, (KU at Lawrence and the KU School of Medicine in Kansas City, and K State University) to become more competitive for securing NIH grant support. This will be achieved by creation of a strong mentoring body (comprised of Dr. Narayan and other established, NIH-funded senior faculty at the three institutions), establishment of committees of internal and outside advisors to the COBRE program, institutionalization of monthly seminar and data presentation meetings, and an annual meeting dedicated to factors important in preparation of NIH grant applications. Three cores, one administrative, and two technical will be established to expedite the research program. The COBRE will receive extensive institutional support in the form of FTEs, new research equipment, and space. The research theme is centered on mechanisms inhibiting replication of pathogenic microbes, with the long-term goal of controlling infectious diseases important in human health. Studies will be focused on identification of genes and gene products that have a seminal role in microbial replication. To find inhibitors for these proteins, we will link up with the COBRE program at KU/Lawrence to exploit resources in combinatorial chemistry and high-throughput screens for inhibitors of the proteins in question. We will also exploit more biological approaches using core support with phage display and aptamer technology, which will be shared among investigators. Further, we will establish core facilities in X-ray crystallography and fermentation for the isolation and determination of the 3-D structures of the proteins, which will be useful for development of potential drugs. Six junior faculty members, two of whom are experienced X-ray crystallographers, have been selected for support for two to three years. The projects of currently selected faculty were based on scientific merit, potential for complementary interaction with other projects, and potential for exploiting the core resources of both COBRE programs. Projects of new junior faculty will be selected and awards made upon recommendation of the internal advisory committee. A portion of the COBRE fund will be used to enhance faculty recruitment packages.